Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition. The current drugs which are used to treat breast cancer focus on the reduction of the tumor size and have proven to be successful. However, currently there are no available treatment options which can effectively inhibit tumor invasion and metastasis. Novel drug strategies therefore are needed to treat this chronic, fatal and incurable condition. Our therapeutic strategy for the treatment of aggressive breast cancer is based on reducing Id-1 expression. In the Phase 1 segment of this Fast-Track proposal our focus will be on developing lead compounds that display a favorable in vivo profile. In Phase II segment of this proposal our lead compounds will be evaluated in multiple in vivo models. We will also develop leads that display a favorable ADME-Tox profile. The ultimate goal of this proposal is to develop a novel therapeutic approach for the treatment of metastatic human breast cancers by down-regulation of Id-1.